The objective of the proposed research is to elucidate the mechanisms controlling steroid hormone biosynthesis in the human placenta, corpus luteum, and fetal adrenals, organs which secrete steroid hormones in large quantities. We shall emphasize studies designed to evaluate the significance of lipoproteins as the source of cholesterol for steroid-hormone biosynthesis. The model systems to be used in this study include: (a) human choriocarcinoma cells in culture, (b) human trophoblastic cells in culture, (c) human granulosa cells in culture and (d) human fetal adrenal cells in culture. The importance of lipoprotein cholesterol versus endogenously synthesized cholesterol as substrate for progesterone biosynthesis in choriocarcinoma cells, trophoblastic cells, and lutenized granulosa cells, and as substrate for dehydroisoandrosterone sulfate and cortisol biosynthesis in fetal adrenal cells will be ascertained. The binding, uptake and degradation of lipoproteins will be studied to establish the pathway of utilization of lipoprotein by these cells. We propose to assess the importance of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) in the economy of these steroid-secreting cells. We will evaluate the rates of uptake and degradation of LDL and HDL. The effect of LDL and HDL on de novo cholesterol synthesis, cholesterol ester synthesis, and steroid hormone biosynthesis will be determined. The interrelationships between control of lipoprotein uptake and control of steroid biosynthesis will be studied by investigating the factors which regulate the cell surface content of lipoprotein receptors, HMG CoA reductase activity, cholesterol side-chain cleavage enzyme activity, and ACAT activity, processes which are important in determining the amount of cholesterol which is available for steroid hormone biosynthesis. The properties of the lipoprotein receptors on the cell surface will be characterized by an analysis of the kinetics of the binding. The role of hormones such as HCG, LH, FSH, prostaglandins, prolactin, ACTH, alpha-MSH, and CLIP in the regulation of steroid biosynthesis in the appropriate cell type will be assessed in terms of a role of these hormones in the stimulation of cholesterol side-chain cleavage activity, and a role for these hormones in determining the rate of uptake of lipoproteins by regulating the numb (Text Truncated - Exceeds Capacity)